Section Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Hannover, Germany.
Neuropsychiatr Dis Treat. 2011;7:341-9. doi: 10.2147/NDT.S10464. Epub 2011 May 30.
In Lambert-Eaton myasthenic syndrome (LEMS), antibodies against presynaptic voltage-gated calcium channels reduce the quantal release of acetylcholine, causing muscle weakness and autonomic dysfunction. More than half of the affected patients have associated small cell lung cancer, and thorough screening for an underlying malignancy is crucial. The mainstay of treatment for LEMS is symptomatic but immunotherapy is needed in more severely affected patients. Symptomatic therapies aim at increasing the concentration of acetylcholine at the muscle endplate. While acetylcholinesterase inhibitors were the first drugs to be used for the amelioration of symptoms, 3,4-diaminopyridine (3,4-DAP, amifampridine) has been shown to be more effective. 3,4-DAP blocks presynaptic potassium channels, thereby prolonging the action potential and increasing presynaptic calcium concentrations. This then results in increased quantal release of acetylcholine. The efficacy of 3,4-DAP for increasing muscle strength and resting compound muscle action potentials has been demonstrated by four placebo-controlled trials. Side effects are usually mild, and the most frequently reported are paresthesias. The most common serious adverse events are epileptic seizures. 3,4-DAP is currently the treatment of choice in patients with Lambert-Eaton myasthenic syndrome.
在 Lambert-Eaton 肌无力综合征 (LEMS) 中，针对突触前电压门控钙通道的抗体减少乙酰胆碱的量子释放，导致肌肉无力和自主神经功能障碍。超过一半的受影响患者伴有小细胞肺癌，彻底筛查潜在恶性肿瘤至关重要。LEMS 的主要治疗方法是对症治疗，但免疫治疗对于病情更严重的患者是必要的。对症治疗旨在增加肌肉终板处乙酰胆碱的浓度。虽然乙酰胆碱酯酶抑制剂是首批用于改善症状的药物，但 3,4-二氨基吡啶 (3,4-DAP，阿米福丁) 已被证明更为有效。3,4-DAP 阻断突触前钾通道，从而延长动作电位并增加突触前钙浓度。这会导致乙酰胆碱的量子释放增加。四项安慰剂对照试验证明了 3,4-DAP 可增加肌肉力量和静息复合肌肉动作电位。副作用通常较轻，最常报告的是感觉异常。最常见的严重不良事件是癫痫发作。3,4-DAP 目前是 Lambert-Eaton 肌无力综合征患者的治疗选择。
